Single Nucleotide Polymorphisms of DNA Base-excision Repair Genes (APE1, OGG1 and XRCC1) Associated with Breast Cancer Risk in a Chinese Population


Altered DNA repair capacity can result in increased susceptibility to cancer. The base excision repair (BER)pathway effectively removes DNA damage caused by ionizing radiation and reactive oxidative species (ROS).In the current study, we analyzed the possible relation of polymorphisms in BER genes, including 8-oxoguanineDNA glycosylase (OGG1), apurinic/apyrimidinic endonuclease 1 (APE1), and X-ray repair cross-complementinggroup 1 protein (XRCC1), with breast cancer risk in Chinese Han women. This case-control study examined 194patients with breast cancer and 245 cancer-free hospitalized control subjects. Single nucleotide polymorphisms(SNPs) of OGG1 (Ser326Cys), XRCC1 (Arg399Gln), and APE1 (Asp148Glu and -141T/G) were genotyped andanalyzed for their association with breast cancer risk using multivariate logistic regression models. We found thatXRCC1 Arg399Gln was significantly associated with an increased risk of breast cancer. Similarly, the XRCC1Gln allele was significantly associated with an elevated risk in postmenopausal women and women with a highBMI (≥ 24 kg/m2). The OGG1 Cys allele provided a significant protective effect against developing cancer inwomen with a low BMI (< 24 kg/m2). When analyzing the combined effects of these alleles on the risk of breastcancer, we found that individuals with ≥ 2 adverse genotypes (XRCC1 399Gln, APE1 148Asp, and OGG1 326Ser)were at a 2.18-fold increased risk of breast cancer (P = 0.027). In conclusion, our data indicate that Chinesewomen with the 399Gln allele of XRCC1 have an increased risk of breast cancer, and the combined effects ofpolymorphisms of BER genes may contribute to tumorigenesis.